APEX2_BOVIN
ID APEX2_BOVIN Reviewed; 514 AA.
AC Q5E9N9; Q58D90;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=DNA-(apurinic or apyrimidinic site) endonuclease 2;
DE EC=3.1.11.2 {ECO:0000250|UniProtKB:P27695};
DE AltName: Full=APEX nuclease 2;
DE AltName: Full=Apurinic-apyrimidinic endonuclease 2;
DE Short=AP endonuclease 2;
GN Name=APEX2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
CC -!- FUNCTION: Functions as a weak apurinic/apyrimidinic (AP)
CC endodeoxyribonuclease in the DNA base excision repair (BER) pathway of
CC DNA lesions induced by oxidative and alkylating agents. Initiates
CC repair of AP sites in DNA by catalyzing hydrolytic incision of the
CC phosphodiester backbone immediately adjacent to the damage, generating
CC a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl
CC ends. Also displays double-stranded DNA 3'-5' exonuclease, 3'-
CC phosphodiesterase activities. Shows robust 3'-5' exonuclease activity
CC on 3'-recessed heteroduplex DNA and is able to remove mismatched
CC nucleotides preferentially. Shows fairly strong 3'-phosphodiesterase
CC activity involved in the removal of 3'-damaged termini formed in DNA by
CC oxidative agents. In the nucleus functions in the PCNA-dependent BER
CC pathway. Required for somatic hypermutation (SHM) and DNA cleavage step
CC of class switch recombination (CSR) of immunoglobulin genes. Required
CC for proper cell cycle progression during proliferation of peripheral
CC lymphocytes (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage in the 3'- to 5'-direction to yield
CC nucleoside 5'-phosphates.; EC=3.1.11.2;
CC Evidence={ECO:0000250|UniProtKB:P27695};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Probably binds two magnesium or manganese ions per subunit.
CC {ECO:0000250};
CC -!- ACTIVITY REGULATION: 3'-5' exonuclease activity is activated by sodium
CC and manganese. 3'-5' exonuclease and 3'-phosphodiesterase activities
CC are stimulated in presence of PCNA (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PCNA; this interaction is triggered by reactive
CC oxygen species and increased by misincorporation of uracil in nuclear
CC DNA. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00764}.
CC Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU00764}. Mitochondrion
CC {ECO:0000250}. Note=Together with PCNA, is redistributed in discrete
CC nuclear foci in presence of oxidative DNA damaging agents.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the DNA repair enzymes AP/ExoA family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAX46554.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BT020881; AAX08898.1; -; mRNA.
DR EMBL; BT021707; AAX46554.1; ALT_FRAME; mRNA.
DR RefSeq; NP_001015577.1; NM_001015577.1.
DR AlphaFoldDB; Q5E9N9; -.
DR SMR; Q5E9N9; -.
DR STRING; 9913.ENSBTAP00000017537; -.
DR PaxDb; Q5E9N9; -.
DR PRIDE; Q5E9N9; -.
DR GeneID; 511790; -.
DR KEGG; bta:511790; -.
DR CTD; 27301; -.
DR eggNOG; KOG1294; Eukaryota.
DR InParanoid; Q5E9N9; -.
DR OrthoDB; 1352540at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0004527; F:exonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR004808; AP_endonuc_1.
DR InterPro; IPR020847; AP_endonuclease_F1_BS.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR010666; Znf_GRF.
DR PANTHER; PTHR22748; PTHR22748; 1.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF06839; zf-GRF; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR TIGRFAMs; TIGR00633; xth; 1.
DR PROSITE; PS00726; AP_NUCLEASE_F1_1; 1.
DR PROSITE; PS51435; AP_NUCLEASE_F1_4; 1.
PE 2: Evidence at transcript level;
KW Cell cycle; Cytoplasm; DNA damage; DNA recombination; DNA repair;
KW DNA-binding; Endonuclease; Exonuclease; Hydrolase; Magnesium;
KW Metal-binding; Mitochondrion; Nuclease; Nucleus; Reference proteome; Zinc;
KW Zinc-finger.
FT CHAIN 1..514
FT /note="DNA-(apurinic or apyrimidinic site) endonuclease 2"
FT /id="PRO_0000200013"
FT ZN_FING 463..511
FT /note="GRF-type"
FT REGION 359..417
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 390..397
FT /note="Required for the colocalization with PCNA in nuclear
FT foci in presence of oxidative-induced DNA damaging agents"
FT /evidence="ECO:0000250"
FT COMPBIAS 379..417
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 156
FT /evidence="ECO:0000250"
FT ACT_SITE 197
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 8
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 48
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 197
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 199
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 303
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT SITE 199
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT SITE 277
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT SITE 304
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250"
FT CONFLICT 369
FT /note="K -> Q (in Ref. 1; AAX46554)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 514 AA; 56938 MW; D22E64035623C993 CRC64;
MLRLVSWNIN GIRSPLQGVR CEEPSSCSAM AMGRILDKLD ADIVCLQETK VTRDVLTEPL
AIIEGYNSYF SFSRNRSGYS GVATFCKDSA TPVAAEEGLS GLLSTQNGDV GCYGNMDDFT
QEELRALDSE GRALLTQHKI CTWEGKEKTL TLINVYCPHA DPGKPERLTF KMRFYRLLQI
RAEALLAAGS HVIILGDLNT AHRPIDHWDA VNMECFEEDP GRKWMDGLLS NLGCESGSHM
GPFIDSYRCF QPKQKGAFTC WSTVSGARHL NYGSRLDYVL GDRTLVIDTF QSSFLLPEVM
GSDHCPVGAV LSVSSVPAKQ CPPLCTCFLP EFAGTQLKIL RFLVHFKQDP VFKQSALQPS
NQTQVHMRKN KARVRSTRSR PSKTGSSRGQ KNLMSYFQPS SSGPQTSNLD LPSLGTLITP
KTSEEDVMAN VVEGQTKASE AKDEKEIRTS FWKSLLGGPS PMPLCGGHRE PCVMRTVKKP
GPNLGRHFYM CARPQGPPTD PSSRCNFFLW SRPS
